STABILITY STUDY OF DRUG-LOADED PROTEINOID MICROSPHERE FORMULATIONS DURING FREEZE-DRYING

Drug-loaded proteinoid microspheres were freeze-dried to facilitate sh ipping and handling and to enable long term storage. Heparin was chose n as the model drug in developing the optimum lyophilization process. The factors influencing the integrity of either heparin-loaded or unlo aded ('empty') proteinoid microspheres during freeze-drying were deter mined, with emphasis on: selecting an optimum freezing and resuspendin g temperature; choosing an appropriate cryoprotectant and its optimum concentration in the formulation; and, designing a suitable method for formulating the microspheres. Freezing at/below -70-degrees-C was fou nd to minimize damage to the microspheres. Addition of sugars, such as trehalose and lactose, as cryoprotectants, further increased the stab ility of the heparin-loaded microspheres during freeze-drying. The opt imum trehalose or lactose concentrations were determined to be 5% (w/v ). Using the optimumized lyophilization process described in this manu script, microspheres remained intact during freeze-drying. The freeze- dried microspheres were stable for at least three months post-lyophili zation.